The goal of this research is to elucidate the underlying mechanisms of aerosol deposition in the pulmonary acinus, as this knowledge is essential to understanding the role of fine particles in respiratory illnesses. Current theories describe aerosol behavior as a dispersive process in the context of reversible acinar flow, but experimental observations show that the behavior of aerosols in the acinus does not follow the basic rules predicted by these theories. Thus, the aerosol deposition process in the acinus needs to be reinterpreted on new theoretical grounds. Recently, with flow visualization studies in excised rat lungs, direct experimental evidence has been obtained that acinar flow can be highly irreversible, exhibiting complex and convoluted stretch-and-fold flow patterns. Based on these findings, it is hypothesized that aerosol behavior in the lung periphery is governed by stretch-and-fold kinematics, rather than dispersive processes. To test this hypothesis, three studies are proposed. (1) Mechanisms governing particle deposition due to stretch-and-fold kinematics will be investigated in depth. Using state of the art numerical techniques, the effects of acinar flow irreversibility associated with the presence of multiple saddle points (present in each expanding alveolus), and asynchronous flow on aerosol deposition will be studied. (2) The cumulative effects of these individual alveolar flow phenomena on the global flow and aerosol behavior will be studied. (3) The comprehensive theoretical framework emerging from these studies (1 and 2) will be tested against animal experiments. Flow visualization and aerosol exposure experiments will be performed on excised rabbit lungs under identical conditions to correlate stretch-and-fold flow patterns with patterns of aerosol deposition and bolus behavior. These studies will provide a solid new foundation to understanding the mechanisms involved in aerosol transport and deposition in the lung periphery, thus shedding light on an important step in the pathogenesis of particle-induced respiratory diseases.